A Ferroptosis-Related Gene Signature for Predicting the Prognosis and Drug Sensitivity of Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and has a high mortality. Ferroptosis, an iron-dependent form of programmed cell death, plays a crucial role in tumor suppression and chemotherapy resistance in cancer. However, the prognostic and clinical values of ferroptosis-related genes (FRGs) in HNSCC remain to be further explored. In the current study, we constructed a ferroptosis-related prognostic model based on the Cancer Genome Atlas database and then explored its prognostic and clinical values in HNSCC via a series of bioinformatics analyses. As a result, we built a four-gene prognostic signature, including FTH1, BNIP3, TRIB3, and SLC2A3. Survival analysis showed that the high-risk group presented significantly poorer overall survival than the low-risk group. Moreover, the ferroptosis-related signature was found to be an independent prognostic predictor with high accuracy in survival prediction for HNSCC. According to immunity analyses, we found that the low-risk group had higher anti-tumor immune infiltration cells and higher expression of immune checkpoint molecules and meanwhile corelated more closely with some anti-tumor immune functions. Meanwhile, all the above results were validated in the independent HSNCC cohort GSE65858. Besides, the signature was found to be remarkably correlated with sensitivity of common chemotherapy drugs for HNSCC patients and the expression levels of signature genes were also significantly associated with drug sensitivity to cancer cells. Overall, we built an effective ferroptosis-related prognostic signature, which could predict the prognosis and help clinicians to perform individualized treatment strategy for HNSCC patients.